Get answers to common questions about IDH1 and CCA, TIBSOVO (ivosidenib tablets), and available resources for patients and healthcare professionals.
About TIBSOVO
What is TIBSOVO (ivosidenib tablets)?
TIBSOVO is an FDA-approved treatment for cholangiocarcinoma (CCA), or bile duct cancer. It is a targeted therapy used to treat locally advanced or metastatic cholangiocarcinoma by inhibiting isocitrate dehydrogenase-1 (IDH1). IDH1 mutations are common early driver mutations in intrahepatic cholangiocarcinoma, occurring in up to 20% of cases in the United States. TIBSOVO is indicated for adult patients with a susceptible IDH1 mutation, as detected by an FDA-approved test, who have been previously treated. TIBSOVO delivered meaningful results in patients with mIDH1 CCA and has a well-characterized safety profile.
What patients are eligible for treatment with TIBSOVO (ivosidenib tablets)?
TIBSOVO is indicated for adult patients with locally advanced or metastatic cholangiocarcinoma (also referred to as bile duct cancer) who have been previously treated and have a susceptible IDH1 mutation as detected by an FDA-approved test. TIBSOVO is also indicated for adult patients with a susceptible IDH1 mutation with newly diagnosed acute myeloid leukemia (AML), relapsed or refractory AML, and relapsed or refractory myelodysplastic syndromes.
What are the recommendations for the use of ivosidenib (TIBSOVO) for cholangiocarcinoma (CCA)?
Ivosidenib (TIBSOVO) was approved for cholangiocarcinoma, or bile duct cancer, in 2021. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend ivosidenib (TIBSOVO) as an NCCN category 1 subsequent-line systemic treatment option for patients with unresectable or metastatic progressive cholangiocarcinoma with IDH1 mutations. The NCCN Guidelines® are reviewed and updated on a continual basis to ensure recommendations account for the most current evidence.
View the most recent and complete version of the guidelines.
Reference: Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Biliary Tract Cancers V.2.2024. © National Comprehensive Cancer Network, Inc., 2024. All rights reserved. Accessed April 19, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
IDH1 & CCA
Why is early testing for patients with cholangiocarcinoma (CCA) important?
IDH1 mutations are common early driver mutations in intrahepatic cholangiocarcinoma (also referred to as bile duct cancer), occurring in up to 20% of cases in the United States. mIDH1 offers an actionable target for treating cholangiocarcinoma, and biomarker testing in combination with targeted therapy, such as TIBSOVO, may improve survival outcomes in cholangiocarcinoma.
How does IDH1 affect cholangiocarcinoma (CCA)?
IDH1 mutations can play a critical role in the development of cholangiocarcinoma, or bile duct cancer. IDH is a key enzyme in the citric acid cycle that catalyzes the conversion of isocitrate to α-ketoglutarate (α-KG). Cancer-associated mutations in IDH1 catalyze the reduction of α-KG to the oncometabolite 2-hydroxyglutarate (2-HG), an accumulation of which leads to oncogenesis. Elevated levels of 2-HG have been observed across multiple tumors with IDH1/2 mutations, including acute myeloid leukemia, glioma, and cholangiocarcinoma. TIBSOVO is a targeted therapy for adult patients with previously treated, locally advanced, or metastatic cholangiocarcinoma with a susceptible IDH1 mutation.
What is the prognosis for cholangiocarcinoma (CCA)?
Cholangiocarcinoma, or bile duct cancer, is the second most common primary liver cancer and is generally associated with a poor prognosis. The 5-year survival rate for metastatic cholangiocarcinoma is 3%. The disease often presents with a lack of specific symptoms, which contributes to 70% of patients getting diagnosed at late stages when the disease is unresectable. In the pivotal trial, TIBSOVO delivered significant improvements in PFS, demonstrating a 63% reduction in the risk of disease progression or death (HR, 0.37 [95% CI, 0.25-0.54]; P<0.0001).
How do I test my patients for IDH1 mutations?
TIBSOVO is indicated for the treatment of adult patients with previously treated, locally advanced, or metastatic cholangiocarcinoma with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by the FDA-approved test. The Ion Torrent™ Oncomine™ DxTarget Test by Thermo Fisher is the FDA-approved companion test to identify patients with IDH1 mutations for whom TIBSOVO may be a treatment option.
How does TIBSOVO (ivosidenib tablets) work to treat cholangiocarcinoma (CCA)?
TIBSOVO is a small molecule inhibitor that selectively inhibits the mutant IDH1 enzyme. mIDH1 is an early driver mutation that occurs in up to 20% of intrahepatic cholangiocarcinoma cases in the United States. TIBSOVO offers a targeted therapy option that could play a role in filling an unmet need in the treatment of advanced cholangiocarcinoma.
Efficacy & pivotal trial
What was the pivotal trial for TIBSOVO (ivosidenib tablets)?
The pivotal trial for TIBSOVO was the ClarIDHy trial, a phase 3, randomized, double-blind, placebo-controlled, multicenter trial. The pivotal trial was one of the largest clinical trials to date of a targeted therapy for cholangiocarcinoma. The primary endpoint was progression-free survival, and secondary endpoints included overall survival, objective response rate, safety, and quality of life.
What endpoints were measured in the pivotal trial for TIBSOVO (ivosidenib tablets)?
The pivotal trial for TIBSOVO was the ClarIDHy trial, a phase 3, randomized, double-blind, placebo-controlled, multicenter trial. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival, objective response rate, safety, and quality of life. TIBSOVO delivered significant improvements in PFS, demonstrating a 63% reduction in the risk of disease progression or death (HR, 0.37 [95% CI, 0.25-0.54]; P<0.0001).
What are the survival rates with TIBSOVO (ivosidenib tablets)?
The primary endpoint of the pivotal trial for TIBSOVO was progression-free survival (PFS). TIBSOVO delivered meaningful improvements in PFS rate at 6 and 12 months, with a PFS rate of 32% at 6 months and 22% at 12 months. None of the patients assigned to placebo had PFS of 6 months or greater.
Do you have data on progression-free survival or overall survival (OS) with TIBSOVO (ivosidenib tablets)?
TIBSOVO delivered significant improvements in progression-free survival. Patients receiving TIBSOVO experienced a 63% reduction in the risk of disease progression or death (HR, 0.37 [95% CI, 0.25-0.54]; P<0.0001). Nearly 1 in 4 patients receiving TIBSOVO remained progression free at 12 months. OS was a secondary endpoint of the pivotal trial. Patients taking TIBSOVO had a numerically higher median OS of 10.3 months (95% CI, 7.8-12.4) compared with 7.5 months with placebo (HR, 0.79 [95% CI, 4.8-11.1]; P=0.093). In the most recent OS analysis, the prespecified rank-preserving structural failure time (RPSFT) model was used to adjust for crossover. The RPSFT-adjusted median OS was 5.1 months with placebo (95% CI, 3.8-7.6 months; HR, 0.49 [95% CI, 0.34-0.70]; 1-sided P<0.001).
This prespecified model, known as rank-preserving structural failure time (RPSFT), is one the most commonly used statistical methods to adjust for treatment switching in oncology trials. This sensitivity analysis was exploratory, and appropriate multiplicity adjustments were not applied.
CI, confidence interval.
Dosing & administration
How is TIBSOVO (ivosidenib tablets) supplied and administered?
TIBSOVO (ivosidenib tablets) offers convenient dosing. The recommended dose of TIBSOVO is 500 mg taken orally once daily until disease progression or unacceptable toxicity. TIBSOVO is available as a 250-mg film-coated tablet, 2 of which should be taken by patients who are prescribed TIBSOVO.
What should patients do if a dose is missed?
If a dose is missed or not taken at the usual time, patients should take the missed dose as soon as possible and at least 12 hours prior to the next scheduled dose. They should return to the normal schedule the following day. They should not take 2 doses within 12 hours. If a dose is vomited, patients should not take a replacement dose; they should wait until the next scheduled dose is due.
Are there any requirements prior to starting patients on TIBSOVO (ivosidenib tablets)?
Prior to treatment initiation, obtain an electrocardiogram and monitor at least once weekly for the first 3 weeks of therapy and then at least once monthly for the duration of therapy. Any abnormalities should be managed promptly. Specific guidance on adverse reactions should be followed if any abnormalities arise.
Safety
What are the most common side effects associated with TIBSOVO (ivosidenib tablets)?
The most common adverse reactions (≥15%) in patients with advanced mIDH1 cholangiocarcinoma were fatigue, nausea, abdominal pain, diarrhea, cough, decreased appetite, ascites, vomiting, anemia, and rash.
What are the most serious side effects associated with TIBSOVO (ivosidenib tablets)?
Patients treated with TIBSOVO can develop QT (QTc) prolongation and ventricular arrhythmias. Concomitant use of TIBSOVO with drugs known to prolong the QTc interval and CYP3A4 inhibitors may increase the risk of QTc interval prolongation. Guillain-Barré syndrome can also develop in patients treated with TIBSOVO. Permanently discontinue in patients who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia, or in patients who are diagnosed with Guillain-Barré syndrome.
How are serious side effects of TIBSOVO (ivosidenib tablets) managed?
Patients treated with TIBSOVO can develop QT (QTc) prolongation and ventricular arrhythmias. Prior to treatment initiation, conduct monitoring of electrocardiograms and electrolytes. In patients with congenital long QTc syndrome, congestive heart failure, or electrolyte abnormalities, or in those who are taking medications known to prolong the QTc interval, more frequent monitoring may be necessary. Interrupt TIBSOVO if QTc increases to >480 msec and <500 msec. Interrupt and reduce TIBSOVO if QTc increases to >500 msec. Permanently discontinue TIBSOVO in patients who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia. Permanently discontinue TIBSOVO in patients who are diagnosed with Guillain-Barré syndrome.
Were any required dose modifications reported during the pivotal trial?
In the pivotal trial, dose interruptions due to adverse reactions occurred in 29% of patients treated with TIBSOVO. The most common (>2%) adverse reactions leading to dose interruption were hyperbilirubinemia, alanine aminotransferase increased, aspartate aminotransferase increased, ascites, and fatigue. Dose reductions of TIBSOVO due to an adverse reaction occurred in 4.1% of patients, and the adverse reactions leading to dose reduction were electrocardiogram QT prolonged (3.3%) and neuropathy peripheral (0.8%). TIBSOVO was permanently discontinued in 7% of patients; the most common adverse reaction leading to permanent discontinuation was acute kidney injury (1.6%).
What was the median relative dose intensity in the pivotal trial?
In the pivotal trial, median relative dose intensity was 100% across all patients. Relative dose intensity is the amount of medication taken over a specific period of time in relation to what was prescribed. There were few occurrences of missed dose modifications, indicating excellent overall compliance.
Access & resources
What resources are available for healthcare professionals for ivosidenib (TIBSOVO)?
The TIBSOVO Product Guide, Flashcard, and Prescribing Information are available as downloadable resources for you and your practice. The TIBSOVO Product Guide provides a comprehensive overview of TIBSOVO efficacy results, recommended dosing, drug-drug interactions, adverse reactions, ordering and distribution network, and patient-specific services. The Ivosidenib (TIBSOVO) Flashcard highlights progression-free survival with ivosidenib (TIBSOVO) and the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommendations.
What resources are available to my patients on TIBSOVO (ivosidenib tablets)?
The TIBSOVO Patient Brochure and Medication Guide are available as downloadable resources for your patients. These resources may be useful to patients and caregivers throughout treatment with TIBSOVO. The TIBSOVO Patient Brochure contains educational information on how TIBSOVO works, what can be expected during treatment, and how to find support.
Does Servier have a patient services program?
ServierONE Patient Support Services for TIBSOVO offers support with insurance coverage and reimbursement, financial assistance to help patients pay for TIBSOVO, and prescription fulfillment through our network of specialty pharmacies and distributors. For more information, visit ServierOne.com or call 1-800-813-5905.
How is TIBSOVO (ivosidenib tablets) ordered and distributed?
TIBSOVO is only available through our specialty distributors and network specialty pharmacies. TIBSOVO is available through specialty distributors for shipment directly to office- or hospital-based pharmacies, and can also ship directly from the specialty pharmacy to your patient’s home or preferred location.
Learn more about the ordering & distribution network for TIBSOVO.
How do healthcare professionals request a visit with a TIBSOVO (ivosidenib tablets) representative?
A registration form is available on our website to request a visit with a TIBSOVO representative. After you have submitted this registration form, a TIBSOVO sales representative will contact you to schedule your appointment.
